Medicine (Austin & Northern Health) - Research Publications
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ItemMaximising data value and avoiding data waste: a validation study in stroke research(AUSTRALASIAN MED PUBL CO LTD, 2019-01-14)OBJECTIVES: To determine the feasibility of linking data from the Australian Stroke Clinical Registry (AuSCR), the National Death Index (NDI), and state-managed databases for hospital admissions and emergency presentations; to evaluate data completeness and concordance between datasets for common variables. DESIGN, SETTING, PARTICIPANTS: Cohort design; probabilistic/deterministic data linkage of merged records for patients treated in hospital for stroke or transient ischaemic attack from New South Wales, Queensland, Victoria, and Western Australia. MAIN OUTCOME MEASURES: Descriptive statistics for data matching success; concordance of demographic variables common to linked databases; sensitivity and specificity of AuSCR in-hospital death data for predicting NDI registrations. RESULTS: Data for 16 214 patients registered in the AuSCR during 2009-2013 were linked with one or more state datasets: 15 482 matches (95%) with hospital admissions data, and 12 902 matches (80%) with emergency department presentations data were made. Concordance of AuSCR and hospital admissions data exceeded 99% for sex, age, in-hospital death (each κ = 0.99), and Indigenous status (κ = 0.83). Of 1498 registrants identified in the AuSCR as dying in hospital, 1440 (96%) were also recorded by the NDI as dying in hospital. In-hospital death in AuSCR data had 98.7% sensitivity and 99.6% specificity for predicting in-hospital death in the NDI. CONCLUSION: We report the first linkage of data from an Australian national clinical quality disease registry with routinely collected data from several national and state government health datasets. Data linkage enriches the clinical registry dataset and provides additional information beyond that for the acute care setting and quality of life at follow-up, allowing clinical outcomes for people with stroke (mortality and hospital contacts) to be more comprehensively assessed.
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ItemDiscovery and Longitudinal Evaluation of Candidate Biomarkers for Ischaemic Stroke by Mass Spectrometry-Based Proteomics(SAGE PUBLICATIONS LTD, 2017-12-20)Application of acute therapies such as thrombolysis for ischaemic stroke (IS) is constrained because of diagnostic uncertainty and the dynamic nature of stroke biology. To investigate changes in blood proteins after stroke and as a result of thrombolysis treatment we performed label-free quantitative proteomics on serum samples using high-resolution mass spectrometry and long high-performance liquid chromatography gradient (5 hours) combined with a 50-cm column to optimise the peptide separation. We identified (false discovery rate [FDR]: 1%) and quantified a total of 574 protein groups from a total of 92 samples from 30 patients. Ten patients were treated by thrombolysis as part of a randomised placebo-controlled trial and up to 5 samples were collected from each individual at different time points after stroke. We identified 26 proteins differently expressed by treatment group (FDR: 5%) and significant changes of expression over time for 23 proteins (FDR: 10%). Molecules such as fibrinogen and C-reactive protein showed expression profiles with a high-potential clinical utility in the acute stroke setting. Protein expression profiles vary acutely in the blood after stroke and have the potential to allow the construction of a stroke clock and to have an impact on IS treatment decision making.
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ItemDifferentiating Childhood Stroke From Mimics in the Emergency Department(LIPPINCOTT WILLIAMS & WILKINS, 2016-10)BACKGROUND AND PURPOSE: Clinical identification of stroke in the pediatric emergency department is critical for improving access to hyperacute therapies. We identified key clinical features associated with childhood stroke or transient ischemic attack compared with mimics. METHODS: Two hundred and eighty consecutive children presenting to the emergency department with mimics, prospectively recruited over 18 months from 2009 to 2010, were compared with 102 children with stroke or transient ischemic attack, prospectively/retrospectively recruited from 2003 to 2010. RESULTS: Cerebrovascular diagnoses included arterial ischemic stroke (55), hemorrhagic stroke (37), and transient ischemic attack (10). Mimic diagnoses included migraine (84), seizures (46), Bell's palsy (29), and conversion disorders (18). Being well in the week before presentation (odds ratio [OR] 5.76, 95% confidence interval [CI] 2.25-14.79), face weakness (OR 2.94, 95% CI 1.19-7.28), arm weakness (OR 8.66, 95% CI, 2.50-30.02), and inability to walk (OR 3.38, 95% CI 1.54-7.42) were independently associated with increased odds of stroke diagnosis. Other symptoms were independently associated with decreased odds of stroke diagnosis (OR 0.28, 95% CI 0.10-0.77). Associations were not observed between seizures or loss of consciousness. Factors associated with stroke differed by arterial and hemorrhagic subtypes. CONCLUSIONS: Being well in the week before presentation, inability to walk, face and arm weakness are associated with increased odds of stroke. The lack of positive or negative association between stroke and seizures or loss of consciousness is an important difference to adults. Pediatric stroke pathways and bedside tools need to factor in differences between children and adults and between stroke subtypes.
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ItemExtrastriate visual cortex reorganizes despite sequential bilateral occipital stroke: implications for vision recovery(FRONTIERS RESEARCH FOUNDATION, 2015-04-28)The extent of visual cortex reorganization following injury remains controversial. We report serial functional magnetic resonance imaging (fMRI) data from a patient with sequential posterior circulation strokes occurring 3 weeks apart, compared with data from an age-matched healthy control subject. At 8 days following a left occipital stroke, contralesional visual cortical activation was within expected striate and extrastriate sites, comparable to that seen in controls. Despite a further infarct in the right (previously unaffected hemisphere), there was evolution of visual cortical reorganization progressed. In this patient, there was evidence of utilization of peri-infarct sites (right-sided) and recruitment of new activation sites in extrastriate cortices, including in the lateral middle and inferior temporal lobes. The changes over time corresponded topographically with the patient's lesion site and its connections. Reorganization of the surviving visual cortex was demonstrated 8 days after the first stroke. Ongoing reorganization in extant cortex was demonstrated at the 6 month scan. We present a summary of mechanisms of recovery following stroke relevant to the visual system. We conclude that mature primary visual cortex displays considerable plasticity and capacity to reorganize, associated with evolution of visual field deficits. We discuss these findings and their implications for therapy within the context of current concepts in visual compensatory and restorative therapies.
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ItemStructural MRI markers of brain aging early after ischemic stroke(LIPPINCOTT WILLIAMS & WILKINS, 2017-07-11)OBJECTIVE: To examine associations between ischemic stroke, vascular risk factors, and MRI markers of brain aging. METHODS: Eighty-one patients (mean age 67.5 ± 13.1 years, 31 left-sided, 61 men) with confirmed first-ever (n = 66) or recurrent (n = 15) ischemic stroke underwent 3T MRI scanning within 6 weeks of symptom onset (mean 26 ± 9 days). Age-matched controls (n = 40) completed identical testing. Multivariate regression analyses examined associations between group membership and MRI markers of brain aging (cortical thickness, total brain volume, white matter hyperintensity [WMH] volume, hippocampal volume), normalized against intracranial volume, and the effects of vascular risk factors on these relationships. RESULTS: First-ever stroke was associated with smaller hippocampal volume (p = 0.025) and greater WMH volume (p = 0.004) relative to controls. Recurrent stroke was in turn associated with smaller hippocampal volume relative to both first-ever stroke (p = 0.017) and controls (p = 0.001). These associations remained significant after adjustment for age, sex, education, and, in stroke patients, infarct volume. Total brain volume was not significantly smaller in first-ever stroke patients than in controls (p = 0.056), but the association became significant after further adjustment for atrial fibrillation (p = 0.036). Cortical thickness and brain volumes did not differ as a function of stroke type, infarct volume, or etiology. CONCLUSIONS: Brain structure is likely to be compromised before ischemic stroke by vascular risk factors. Smaller hippocampal and total brain volumes and increased WMH load represent proxies for underlying vascular brain injury.
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ItemSTROKOG (stroke and cognition consortium): An international consortium to examine the epidemiology, diagnosis, and treatment of neurocognitive disorders in relation to cerebrovascular disease.(Wiley, 2017)INTRODUCTION: The Stroke and Cognition consortium (STROKOG) aims to facilitate a better understanding of the determinants of vascular contributions to cognitive disorders and help improve the diagnosis and treatment of vascular cognitive disorders (VCD). METHODS: Longitudinal studies with ≥75 participants who had suffered or were at risk of stroke or TIA and which evaluated cognitive function were invited to join STROKOG. The consortium will facilitate projects investigating rates and patterns of cognitive decline, risk factors for VCD, and biomarkers of vascular dementia. RESULTS: Currently, STROKOG includes 25 (21 published) studies, with 12,092 participants from five continents. The duration of follow-up ranges from 3 months to 21 years. DISCUSSION: Although data harmonization will be a key challenge, STROKOG is in a unique position to reuse and combine international cohort data and fully explore patient level characteristics and outcomes. STROKOG could potentially transform our understanding of VCD and have a worldwide impact on promoting better vascular cognitive outcomes.
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ItemIntegrating acute stroke telemedicine consultations into specialists' usual practice: a qualitative analysis comparing the experience of Australia and the United Kingdom(BMC, 2017-11-21)BACKGROUND: Stroke telemedicine can reduce healthcare inequities by increasing access to specialists. Successful telemedicine networks require specialists adapting clinical practice to provide remote consultations. Variation in experiences of specialists between different countries is unknown. To support future implementation, we compared perceptions of Australian and United Kingdom specialists providing remote acute stroke consultations. METHODS: Specialist participants were identified using purposive sampling from two new services: Australia's Victorian Stroke Telemedicine Program (n = 6; 2010-13) and the United Kingdom's Cumbria and Lancashire telestroke network (n = 5; 2010-2012). Semi-structured interviews were conducted pre- and post-implementation, recorded and transcribed verbatim. Deductive thematic and content analysis (NVivo) was undertaken by two independent coders using Normalisation Process Theory to explore integration of telemedicine into practice. Agreement between coders was M = 91%, SD = 9 and weighted average κ = 0.70. RESULTS: Cross-cultural similarities and differences were found. In both countries, specialists described old and new consulting practices, the purpose and value of telemedicine systems, and concerns regarding confidence in the assessment and diagnostic skills of unknown colleagues requesting telemedicine support. Australian specialists discussed how remote consultations impacted on usual roles and suggested future improvements, while United Kingdom specialists discussed system governance, policy and procedures. CONCLUSION: Australian and United Kingdom specialists reported telemedicine required changes in work practice and development of new skills. Both groups described potential for improvements in stroke telemedicine systems with Australian specialists more focused on role change and the United Kingdom on system governance issues. Future research should examine if cross-cultural variation reflects different models of care and extends to other networks.
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ItemHospital organizational context and delivery of evidence-based stroke care: a cross-sectional study(BMC, 2019-01-18)BACKGROUND: Organizational context is one factor influencing the translation of evidence into practice, but data pertaining to patients with acute stroke are limited. We aimed to determine the associations of organizational context in relation to four important evidence-based stroke care processes. METHODS: This was a mixed methods cross-sectional study. Among 19 hospitals in Queensland, Australia, a survey was conducted of the perceptions of stroke clinicians about their work using the Alberta Context Tool (ACT), a validated measure covering 10 concepts of organizational context, and with additional stroke-specific contextual questions. These data were linked to the Australian Stroke Clinical Registry (AuSCR) to determine the relationship with receipt of evidence-based acute stroke care (acute stroke unit admission, use of thrombolysis for those with acute ischemic stroke, receipt of a written care plan on discharge, and prescription of antihypertensive medications on discharge) using quantile regression. Exploratory cluster analysis was used to categorize hospitals into high and low context groups based on all of the 10 ACT concepts. Differences in adherence to care processes between the two groups were examined. RESULTS: A total of 215 clinicians completed the survey (50% nurses, 37% allied health staff, 10% medical practitioners), with 81% being in their current role for at least 1 year. There was good reliability (∞ 0.83) within the cohort to allow pooling of professional groups. Greater ACT scores, especially for social capital (μ 9.00, 95% confidence interval [CI] 4.86 to 13.14) and culture (μ 7.33, 95% CI 2.05 to 12.62), were associated with more patients receiving stroke unit care. There was no correlation between ACT concepts and other care processes. Working within higher compared to lower context environments was associated with greater proportions of patients receiving stroke unit care (88.5% vs. 69.0%) and being prescribed antihypertensive medication at discharge (62.5% vs. 52.0%). Staff from higher context hospitals were more likely to value medical and/or nursing leadership and stroke care protocols. CONCLUSIONS: Overall organizational context, and in particular aspects of culture and social capital, are associated with the delivery of some components of evidence-based stroke care, offering insights into potential pathways for improving the implementation of proven therapies.
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ItemHyperacute changes in blood mRNA expression profiles of rats after middle cerebral artery occlusion: Towards a stroke time signature.(Public Library of Science (PLoS), 2018)Stroke evolution is a highly dynamic but variable disease which makes clinical decision making difficult. Biomarker discovery programs intended to aid clinical decision making have however largely ignored the rapidity of stroke evolution. We have used gene array technology to determine blood mRNA expression changes over the first day after stroke in rats. Blood samples were collected from 8 male spontaneously hypertensive rats at 0, 1, 2, 3, 6 and 24h post stroke induction by middle cerebral artery occlusion. RNA was extracted from whole blood stabilized in PAXgene tubes and mRNA expression was detected by oligonucleotide Affymetrix microarray. Using a pairwise comparison model, 1932 genes were identified to vary significantly over time (p≤0.5x10(-7)) within 24h after stroke. Some of the top20 most changed genes are already known to be relevant to the ischemic stroke physiopathology (e.g. Il-1R, Nos2, Prok2). Cluster analysis showed multiple stereotyped and time dependent profiles of gene expression. Direction and rate of change of expression for some profiles varied dramatically during these 24h. Profiles with potential clinical utility including hyper acute or acute transient upregulation (with expression peaking from 2 to 6h after stroke and normalisation by 24h) were identified. We found that blood gene expression varies rapidly and stereotypically after stroke in rats. Previous researchers have often missed the optimum time for biomarker measurement. Temporally overlapping profiles have the potential to provide a biological "stroke clock" able to tell the clinician how far an individual stroke has evolved.
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ItemMulticenter, Prospective, Controlled, Before-and-After, Quality Improvement Study (Stroke123) of Acute Stroke Care(LIPPINCOTT WILLIAMS & WILKINS, 2019-06)Background and Purpose- Hospital uptake of evidence-based stroke care is variable. We aimed to determine the impact of a multicomponent program involving financial incentives and quality improvement interventions, on stroke care processes. Methods- A prospective study of interventions to improve clinical care quality indicators at 19 hospitals in Queensland, Australia, during 2010 to 2015, compared with historical controls and 23 other Australian hospitals. After baseline routine audit and feedback (control phase, 30 months), interventions involving financial incentives (21 months) and then addition of externally facilitated quality improvement workshops with action plan development (9 months) were implemented. Postintervention phase was 13 months. Data were obtained for the analysis from a previous continuous audit in Queensland and subsequently the Australian Stroke Clinical Registry. Primary outcome: change in median composite score for adherence to ≤8 indicators. Secondary outcomes: change in adherence to self-selected indicators addressed in action plans and 4 national indicators compared with other Australian hospitals. Multivariable analyses with adjustment for clustered data. Results- There were 17 502 patients from the intervention sites (median age, 74 years; 46% women) and 20 484 patients from other Australian hospitals. Patient characteristics were similar between groups. There was an 18% improvement in the primary outcome across the study periods (95% CI, 12%-24%). The largest improvement was following introduction of financial incentives (14%; 95% CI, 8%-20%), while indicators addressed in action plans provided an 8% improvement (95% CI, 1%-17%). The national score (4 indicators) improved by 17% (95% CI, 13%-20%) versus 0% change in other Australian hospitals (95% CI, -0.03 to 0.03). Access to stroke units improved more in Queensland than in other Australian hospitals ( P<0.001). Conclusions- The quality improvement interventions significantly improved clinical practice. The findings were primarily driven by financial incentives, but were also contributed to by the externally facilitated, quality improvement workshops. Assessment in other regions is warranted.